2020
TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Gorelick F, Nathanson MH. TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells. Journal Of Clinical Investigation 2020, 130: 2199-2201. PMID: 32281947, PMCID: PMC7190901, DOI: 10.1172/jci136525.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsCalcium signalingAcinar cellsPlasma membrane calcium channelsGenetic deletion modelsMembrane calcium channelsCytosolic calcium levelsCell culture systemDeletion modelTransient receptor potential vanilloidPathogenesis of pancreatitisSignalingCulture systemCellsPathwayStimulation pathwayCalcium channels
2019
Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.
Gukovskaya AS, Gorelick FS, Groblewski GE, Mareninova OA, Lugea A, Antonucci L, Waldron RT, Habtezion A, Karin M, Pandol SJ, Gukovsky I. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas 2019, 48: 459-470. PMID: 30973461, PMCID: PMC6461375, DOI: 10.1097/mpa.0000000000001298.Peer-Reviewed Original ResearchConceptsOrganelle dysfunctionCell death responseSecretion of proteinsAcinar cell homeostasisOrganelle disordersNascent proteinsDysfunctional organellesDeath responseAccessory proteinsVesicular compartmentsEndosomal pathwayCell homeostasisAcute pancreatitisEndoplasmic reticulumProtein synthesisCells triggersPancreatic acinar cellsLethal inflammatory diseaseDigestive enzymesCell constituentsRecent insightsDistinct mechanismsProteinOrganellesAcinar cell injury
2017
The serum protein renalase reduces injury in experimental pancreatitis
Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.m117.789776.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersCalcium SignalingCarbacholCell LineCeruletideEnzyme ActivationFluorescent Antibody Technique, IndirectGene Expression Regulation, EnzymologicHumansHypertensionLigandsMembrane Transport ModulatorsMiceMice, KnockoutMonoamine OxidasePancreasPancreatitisPlasma Membrane Calcium-Transporting ATPasesRecombinant Fusion ProteinsTaurolithocholic AcidConceptsRecombinant human renalaseAcute pancreatitisAcute injuryCell injuryAcinar cell injuryHuman acinar cellsCytosolic calcium levelsPlasma membrane calcium ATPasePancreatitis onsetIschemic injuryWT micePathological increaseHistological changesProtective effectSevere diseaseMurine modelMembrane calcium ATPasePancreatitisCalcium levelsExperimental pancreatitisBile acidsTissue damageRenalaseInjuryCerulein modelHuman Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis
Lugea A, Waldron RT, Mareninova OA, Shalbueva N, Deng N, Su HY, Thomas DD, Jones EK, Messenger SW, Yang J, Hu C, Gukovsky I, Liu Z, Groblewski GE, Gukovskaya AS, Gorelick FS, Pandol SJ. Human Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis. American Journal Of Pathology 2017, 187: 2726-2743. PMID: 28935577, PMCID: PMC5718097, DOI: 10.1016/j.ajpath.2017.08.017.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsCadaverCell Culture TechniquesCells, CulturedHumansPancreasPancreatitisProteomicsConceptsOrganellar morphologyEndoplasmic reticulum stressProteomic characterizationEndolysosomal functionProteomic analysisMolecular mechanismsMitochondrial depolarizationTaurolithocholic acidPhysiological functionsMuscarinic acetylcholine receptor M3Acute pancreatitis patientsBile acid taurolithocholic acidMacrophage inhibitory factorReticulum stressDigestive enzymesMuscarinic agonist carbacholTumor necrosis factorPhysiological responsesSimilar pathological responsesAcinar preparationsAcinar cell responsesCell viabilityInflammatory mediatorsSimilar mechanismPancreatitis patients
2016
Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
Srinivasan P, Thrower EC, Gorelick FS, Said HM. Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AJP Gastrointestinal And Liver Physiology 2016, 310: g874-g883. PMID: 26999808, PMCID: PMC4888549, DOI: 10.1152/ajpgi.00461.2015.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnion Transport ProteinsBiological TransportCarcinogensCell LineHistonesMiceMice, Inbred C57BLMitochondrial Membrane Transport ProteinsMitochondrial ProteinsNitrosaminesPancreasPromoter Regions, GeneticProtein Processing, Post-TranslationalRNA, MessengerThiamine PyrophosphateTobacco Smoke PollutionConceptsPancreatic acinar cellsThiamin pyrophosphateEffect of NNKSpecific plasma membrane transporterPlasma membrane transportersNormal mitochondrial functionMTPPT proteinHistone modificationsH3K4 trimethylationNuclear RNAH3K9 acetylationHeterogenous nuclear RNAMethylation profilesPromoter activityMitochondrial functionChronic exposureReduced expressionNormal metabolismTranscriptionΑ7 nicotinic acetylcholine receptorAcetylcholine receptorsCigarette smoke toxinsTransportersAcinar cellsUptake process
2015
Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells
Srinivasan P, Thrower EC, Loganathan G, Balamurugan AN, Subramanian VS, Gorelick FS, Said HM. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells. PLOS ONE 2015, 10: e0143575. PMID: 26633299, PMCID: PMC4669105, DOI: 10.1371/journal.pone.0143575.Peer-Reviewed Original ResearchConceptsHuman pancreatic acinar cellsPancreatic acinar cellsNormal cellular functionThiamin uptakeTHTR-1Chronic exposureMurine pancreatic acinar cellsThiamin uptake processCellular functionsAcinar cellsThiamin pyrophosphokinaseMolecular biologyThiamin transporter-1Mouse pancreatic acinar cellsSpecific carrier-mediated processMitochondrial dysfunctionTHTR-2Chronic nicotine exposureTransporter 1Oxidative stressProteinExpressionNicotine impairsUptake processNicotine exposure
2014
Low pH enhances connexin32 degradation in the pancreatic acinar cell
Reed AM, Kolodecik T, Husain SZ, Gorelick FS. Low pH enhances connexin32 degradation in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2014, 307: g24-g32. PMID: 24812055, PMCID: PMC4080162, DOI: 10.1152/ajpgi.00010.2014.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsGap junctionsGap junctional intercellular communicationIntercellular communicationRat pancreatic acinar cellsPredominant gap junction proteinExtracellular pHAcute pancreatitisJunctional intercellular communicationClinical conditionsGap junction proteinJunction proteinsGap junctional intracellular communicationAutophagic pathwayFirst evidenceCellsIntracellular communicationConnexin32Pancreatitis
2013
Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells
Messenger SW, Thomas DD, Falkowski MA, Byrne JA, Gorelick FS, Groblewski GE. Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2013, 305: g439-g452. PMID: 23868405, PMCID: PMC3761242, DOI: 10.1152/ajpgi.00143.2013.Peer-Reviewed Original ResearchConceptsImmature secretory granulesApical exocytosisTumor protein D52Endosomal compartmentsEndolysosomal compartmentsMinor regulated pathwayZymogen granule formationAcinar cellsEndosomal intermediatesISG maturationSerine 136Phosphorylation sitesTrans-GolgiSecretory pathwayAspartate substitutionContent proteinsRegulatory proteinsBrefeldin ASynaptotagmin-1Molecular componentsPancreatic acinar cellsGranule formationExocytosisLysosomal membraneLAMP1
2012
Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells
Kolodecik TR, Shugrue CA, Thrower EC, Levin LR, Buck J, Gorelick FS. Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells. PLOS ONE 2012, 7: e41320. PMID: 22844459, PMCID: PMC3402497, DOI: 10.1371/journal.pone.0041320.Peer-Reviewed Original ResearchConceptsProtein kinase AActivation of SACZymogen activationPancreatic acinar cellsSpecific subcellular domainsAcinar cellsActivation of zymogensCerulein-treated cellsSubcellular domainsDownstream targetsKinase ASAC activitySAC inhibitorAdenylyl cyclaseDistinct mechanismsAdenylyl cyclase inhibitorElevates levelsApical regionAmylase secretionCellsActivationAcinar cell vacuolizationCAMPCAMP accumulationCell vacuolization